← Back to Search

Enzyme

Calaspargase + Cobimetinib for Pancreatic Cancer

Phase 1

Recruiting

Led By Charles D Lopez

Research Sponsored by OHSU Knight Cancer Institute

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Histologically or cytologically-proven adenocarcinoma of the exocrine pancreas with locally advanced or metastatic disease

Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

Must not have

Known severe hypersensitivity to calaspargase pegol-mknl (or equivalent) or to cobimetinib (or equivalent), or to any excipient of these medicinal products, or history of allergic reactions attributed to compounds of similar chemical or biologic composition to calaspargase pego-mknl or cobimetinib

Use of known strong CYP3A inhibitors (e.g., itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir), known strong CYP3A inducers (e.g., phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate CYP3A inducers (e.g., bosentan, efavirenz, modafinil) within 7 days of prior to initiating study treatment or on going requirement for these medications

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 30 days after last dose of study intervention

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing the safety and best dose of two drugs to treat pancreatic cancer. One drug, calaspargase pegol-mknl, starves cancer cells of a nutrient they need. The other drug, cobimetinib, attacks a protein that stimulates cancer cell growth.

Who is the study for?

Adults with advanced or metastatic pancreatic cancer who have not responded to, cannot tolerate, or refused standard treatments like Gemcitabine-based therapy or FOLFORINOX. They must be in relatively good health (ECOG 0-2), have acceptable blood counts and organ function, and agree to use non-hormonal contraception. Pregnant women, those with certain heart conditions, severe allergies to trial drugs, uncontrolled medical issues, or recent other cancer therapies are excluded.

What is being tested?

The trial is testing the combination of Calaspargase Pegol-mknl and Cobimetinib for safety and optimal dosing against pancreatic cancer that has spread. Calaspargase Pegol-mknl deprives cancer cells of a needed amino acid while Cobimetinib blocks a protein that helps these cells grow.

What are the potential side effects?

Potential side effects include allergic reactions to the medications used; changes in blood counts leading to increased risk of infections; liver problems indicated by altered lab tests; fatigue; digestive issues such as nausea and vomiting; potential heart rhythm problems.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

My pancreatic cancer is confirmed and has spread.

Select...

I can take care of myself and am up and about more than half of the day.

Select...

I am 18 years old or older.

Select...

I have at least one tumor that can be biopsied.

Select...

My hemoglobin level is at least 9.0 g/dL without recent blood transfusions.

Select...

My kidney function, measured by creatinine levels, is within the normal range.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I am allergic to calaspargase pegol-mknl, cobimetinib, or similar drugs.

Select...

I am not taking any strong or moderate drugs that affect liver enzymes.

Select...

My high blood pressure is not under control.

Select...

I have a history of or current issues with specific eye conditions.

Select...

I have a history of chronic or recurrent pancreatitis, or currently have signs of acute pancreatitis.

Select...

I have a condition that affects my ability to swallow or absorb pills.

Select...

I have been treated with L-asparaginase before.

Select...

I haven't had serious heart issues or a stroke in the last 6 months.

Select...

I do not have an ongoing serious infection that isn't getting better with treatment.

Select...

I do not have any severe or uncontrolled health conditions like diabetes or high blood pressure.

Select...

I am not on any other cancer treatments or live vaccines while on the study medication.

Select...

I have a serious blood clotting issue that isn't under control.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 30 days after last dose of study intervention

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 30 days after last dose of study intervention

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 30 days after last dose of study intervention for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Incidence of dose-limiting toxicities (DLTs)

Secondary study objectives

Disease control rate (DCR)

Incidence of treatment-emergent adverse events (AEs) and serious AEs

Mean plasma asparaginase activity

+1 more

Other study objectives

Therapy induced changes in the tumor and tumor ecosystem

Side effects data

From 2021 Phase 3 trial • 166 Patients • NCT00671034

64%

Neutrophil count decreased

54%

Febrile neutropenia

43%

Platelet count decreased

43%

Infections and infestations - Other, specify

36%

Alanine aminotransferase increased

36%

Hypokalemia

30%

Hyperglycemia

28%

White blood cell decreased

26%

Anemia

23%

Mucositis oral

19%

Hypocalcemia

19%

Anaphylaxis

17%

Hyponatremia

17%

Blood bilirubin increased

16%

Abdominal pain

16%

Anorexia

14%

Aspartate aminotransferase increased

13%

Nausea

13%

Hyperkalemia

13%

Hypophosphatemia

12%

Pancreatitis

12%

Hypoalbuminemia

12%

Serum amylase increased

12%

Diarrhea

12%

Lung infection

12%

Hypoxia

10%

Lipase increased

10%

Hypotension

Oral pain

Pleural effusion

Enterocolitis infectious

Vomiting

Hypertriglyceridemia

Thromboembolic event

Pain

Weight loss

Back pain

Death NOS

Fibrinogen decreased

Urinary tract infection

Dyspnea

GGT increased

Fatigue

Activated partial thromboplastin time prolonged

Hypertension

Sepsis

Skin infection

Alkaline phosphatase increased

Pharyngolaryngeal pain

Epistaxis

Upper respiratory infection

Generalized muscle weakness

Pain in extremity

Fever

Acidosis

Catheter related infection

Avascular necrosis

Dehydration

Glucose intolerance

Hyperuricemia

Nervous system disorders - Other, specify

Anal pain

Cholesterol high

Depression

Acute kidney injury

Adult respiratory distress syndrome

Oral hemorrhage

Non-cardiac chest pain

Pharyngitis

Creatinine increased

Hypercalcemia

Tumor lysis syndrome

Arthralgia

Rash maculo-papular

Vascular disorders - Other, specify

Dysphasia

Encephalopathy

Headache

Typhlitis

Seizure

Syncope

Agitation

Dizziness

Myositis

Anxiety

Esophagitis

Irritability

Hematoma

Ascites

Investigations - Other, specify

Tremor

Pancreatic necrosis

Infective myositis

INR increased

Peripheral nerve infection

Wound infection

Injury, poisoning and procedural complications - Other, specify

Purpura

Lymphocyte count decreased

Joint effusion

Muscle weakness right-sided

Musculoskeletal and connective tissue disorder - Other, specify

Chronic kidney disease

Blood and lymphatic system disorders - Other, specify

Disseminated intravascular coagulation

Ileus

Anorectal infection

Lip infection

Paronychia

Scrotal infection

Sinusitis

Weight gain

Cerebrospinal fluid leakage

Depressed level of consciousness

Intracranial hemorrhage

Pneumonitis

Psychiatric disorders - Other, specify

Personality change

CPK increased

Leukoencephalopathy

Colitis

Mucosal infection

Pharyngeal mucositis

Alkalosis

Bone pain

Abducens nerve disorder

Psychosis

Neuralgia

Suicidal ideation

Hemolysis

Supraventricular tachycardia

Left ventricular systolic dysfunction

Middle ear inflammation

Eye disorders - Other, specify

Retinal detachment

Vasovagal reaction

Pruritus

100%

80%

60%

40%

20%

Study treatment Arm

Arm I (Calaspargase Pegol 2100)

Arm II (Calaspargase Pegol 2500)

Arm III (Pegaspargase 2500)

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Treatment (calaspargase pegol-mknl, cobimetinib)Experimental Treatment3 Interventions

Patients receive calaspargase pegol-mknl IV over 1 hour on day 1 and cobimetinib PO QD on days 1-14. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Biopsy

2014

Completed Phase 4

~1150

Calaspargase Pegol-mknl

2008

Completed Phase 3

~170